We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a ...previously validated protein panel for early-stage PDAC.
A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated.
Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval CI = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02).
A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
Abstract Context Marked unexplained national variations in incidence rates of kidney cancer have been observed for decades in Europe. Objective To investigate geographic variations at the regional ...level and identify European regions with high incidence rates of kidney cancer. Evidence acquisition Regional- and national-level incidence data were extracted from the Cancer Incidence in Five Continents databases, local cancer registry databases, and local published reports. World population age-standardised rates (ASRs) were calculated for the periods 2003–2007 and 1988–1992. Rates by period and sex were compared using map visualisation. Evidence synthesis During 2003–2007, the highest ASR was found in the Plzen region, Czech Republic (31.4/100 000 person-years in men). Other regions of the Czech Republic had ASRs of 18.6–27.5/100 000 in men, with a tendency for higher rates in regions south of Prague. Surrounding regions, including eastern Germany and regions of Slovakia and Austria, had medium-to-high incidence rates (13.0–16.8/100 000 in men). Three other areas in Europe showed higher incidence rates in men compared with the rest of the continent: Lithuania, Estonia, Latvia, and Belarus (15.0–17.6/100 000); Iceland (13.5/100 000), and northern Italy (up to 16.0/100 000). Similar regional differences were observed among women, with rates approximately half of those observed in men in the same region. In general, these regional geographic variations remained stable over the periods 1988–1992 and 2003–2007, although higher incidence rates were detected in the Baltic countries in 2003–2007. Conclusions Several European regions show particularly high rates of kidney cancer incidence. Large variations were observed within countries covered by national health-care systems, implying that overdetection is not the major factor. Patient summary We present regional geographic variations in kidney cancer incidence rates in Europe. We highlight several regions with high incidence rates where further studies should be conducted for cancer control and prevention.
We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly ...associated loci (P < 5 × 10
), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10
). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10
) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) ...prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA).
Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs).
HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1).
A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.
Studies of the impact of long-term exposure to outdoor air pollution on the prevalence of respiratory symptoms and lung function in children have yielded mixed results, partly related to differences ...in study design, exposure assessment, confounder selection and data analysis. We assembled respiratory health and exposure data for >45,000 children from comparable cross-sectional studies in 12 countries. 11 respiratory symptoms were selected, for which comparable questions were asked. Spirometry was performed in about half of the children. Exposure to air pollution was mainly characterised by annual average concentrations of particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM(10)) measured at fixed sites within the study areas. Positive associations were found between the average PM(10) concentration and the prevalence of phlegm (OR per 10 μg · m(-3) 1.15, 95% CI 1.02-1.30), hay fever (OR 1.20, 95% CI 0.99-1.46), bronchitis (OR 1.08, 95% CI 0.98-1.19), morning cough (OR 1.15, 95% CI 1.02-1.29) and nocturnal cough (OR 1.13, 95% CI 0.98-1.29). There were no associations with diagnosed asthma or asthma symptoms. PM(10) was not associated with lung function across all studies combined. Our study adds to the evidence that long-term exposure to outdoor air pollution, characterised by the concentration of PM(10), is associated with increased respiratory symptoms.
Background: Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for ...Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A). Objectives: We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods: Using questionnaire data, we classified subjects as predominant solid-fuel users (e. g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center. Results: Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49-1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73-6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06-1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Conclusions: Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations.
Background
The COVID‐19 pandemic has posed unprecedented challenges, particularly for healthcare workers (HCWs). The prolonged struggles exposed the HCWs to a variety of stressors, potentially ...leading to burnout. Emotional exhaustion is widely recognized as the core component of burnout. This research aims to conceptualize and develop an emotional exhaustion screening questionnaire through literature review, validation, and accuracy testing.
Method
A literature review of questionnaires and extraction of items on emotional exhaustion were performed in June 2022. We proceed with the face validity of the items by experts. The items with good content validity ratio and index were selected and reworded to suit the context of HCWs working during the COVID‐19 pandemic. A pilot test of the questionnaire was done in the Central University Hospital of Asturias (HUCA) from October to December 2022 with a sample of 148 HCWs from the ORCHESTRA cohort to determine its reliability, convergent validity, and accuracy.
Results
Our literature review identified 15 validated questionnaires. After exclusion, 32 items were sent for content validation by experts, yielding five final items that proceeded with the pilot test. Resulting in a Cronbach's alpha‐coefficient of .83 for the scale and .78 for dichotomous responses, demonstrating good internal consistency and convergent validity. The result of our accuracy test yielded sensitivity (90.6%) and specificity (91.6%) for the OEEQ scale; and sensitivity (88.7%) and specificity (89.5%) for OEEQ dichotomous responses.
Conclusion
This study developed and validated the ORCHESTRA Emotional Exhaustion Questionnaire, demonstrating the questionnaire's clarity, relevance, and comprehensibility in screening emotional exhaustion among HCWs.
We investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine ...doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months.
Persistence of vaccine immunization is key for COVID-19 prevention.
We investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements.
We observed a progressively decreasing difference in serologic levels from <30 days to 210-240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference 95% confidence interval (CI) 0.78-0.85. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07-1.10) and 1.04 (95% CI 1.03-1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56-1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75-0.92) and mixed vaccines (RR 0.61, 95% CI 0.51-0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40-0.54).
Age, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.
The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort.
...We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months' serology within one cohort.
: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (
= 0.01), age (RR = 0.87, 95% CI = 0.86-0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97-0.98), previous infection (3.03, 95% CI = 2.92-3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09-1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39-1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44-0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12-1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1-7 months,
for trend 0.005).
Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.
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